TY  - JOUR
A1  - Wilcox, Mark H.
A1  - Cornely, Oliver Andreas
A1  - Guery, Benoit
A1  - Longshaw, Chris
A1  - Georgopali, Areti
A1  - Karas, Andreas
A1  - Kazeem, Gbenga
A1  - Palacios Fabrega, Jose Alejandro
A1  - Vehreschild, Maria J. G. T.
T1  - Microbiological characterization and clinical outcomes after extended-pulsed fidaxomicin treatment for Clostridioides difficile infection in the extend study
T2  - Open Forum Infectious Diseases
N2  - Background: Clostridioides (Clostridium) difficile infection (CDI) is diagnosed using clinical signs and symptoms plus positive laboratory tests. Recurrence of CDI after treatment is common, and coinfection with other enteric pathogens may influence clinical outcomes.
Methods: We aimed to assess rates of C difficile positivity, by enzyme-linked immunosorbent assay (ELISA) toxin A/B and BioFire FilmArray, and the effect of enteric coinfection on clinical outcomes, using samples from the EXTEND study of extended-pulsed fidaxomicin (EPFX) versus standard vancomycin.
Results: All 356 randomized and treated patients tested positive for C difficile toxin A/B by local tests; a majority (225 of 356, 63.2%) also tested positive by both ELISA and BioFire. Most stool samples taken at screening tested positive for C difficile only using BioFire (EPFX: 112 of 165, 69.7%; vancomycin: 118 of 162, 72.8%). Of the 5 patients who failed treatment and had stool samples available, all (1) had tested negative for C difficile by BioFire at screening and (2) were negative by ELISA at time of treatment failure. When analyzed by BioFire results at screening, rates of sustained clinical cure at 30 days after end of treatment were numerically higher with EPFX than with vancomycin for almost all patients, except for those who tested negative for C difficile but positive for another pathogen. However, these outcome differences by presence of coinfection did not reach statistical significance. Whole-genome sequencing analysis determined that 20 of 26 paired samples from patients with recurrence were reinfections with the same C difficile strain.
Conclusions: Testing for presence of copathogens in clinical trials of antibiotics could help to explain clinical failures.
KW  - Clostridioides difficile
KW  - fidaxomicin
KW  - gut microbiota
KW  - infection
KW  - vancomycin
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54480
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-544807
SN  - 2328-8957
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
VL  - 6
IS  - 11, ofz436
SP  - 1
EP  - 7
PB  - Oxford University Press
CY  - Oxford
ER  -